Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Comparative evaluation of absorbed dose estimates derived from passive dosimetry measurements to those derived from biological monitoring: Validation of exposure monitoring methodologies

Abstract

Passive dosimetry (PD) methods for measuring and estimating exposure to agricultural workers (i.e., persons handling agricultural chemicals and working in treated crops) have been in use since the 1950s. A large number of studies were conducted in the 1950s through 1970s to characterize exposure. Since the 1980s quantitative dermal PD methods are used in conjunction with inhalation PD methods to measure whole-body exposure. These exposure or absorbed dose estimates are then compared to “no effect” exposure levels for hazards identified in toxicology studies, and have become the standard for risk assessment for regulatory agencies. The PD methods used have never been validated. Validation in the context of human exposure monitoring methods means that a method has been shown to measure accurately a delivered dose in humans. The most practical alternative to isolating parts of the body for validating recovery methods is to utilize field exposure studies in which concurrent or consecutive measurements of exposure and absorbed dose have been made with PD and biomonitoring in the same cohorts of individuals. This ensures that a direct comparison can be made between the two estimates of absorbed dose, one derived from PD and the other from biomonitoring. There are several studies available (published and proprietary) employing both of these approaches. Reports involving 14 concurrent or consecutive PD-biomonitoring studies were quantitatively evaluated with 18 different methods of application or reentry scenarios for eight different active ingredients for which measured human kinetics and dermal absorption data existed. This evaluation demonstrated that the total absorbed dose estimated using PD for important handler and reentry scenarios is generally similar to the measurements for those same scenarios made using human urinary biomonitoring methods. The statistical analysis of individual worker PD:biomonitoring ratios showed them to be significantly correlated in these studies. The PD techniques currently employed yield a reproducible, standard methodology that is valid and reliably quantifies exposure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Barr D.B., and Angerer J. Potential uses of biomonitoring data: a case study using the organophosphorus pesticides chlorpyrifos and malathion. Environ Health Perspect 2006 [minimonograph].

  • Batchelor G.S., and Walker K.C. Health hazards involved in the use of parathion in fruit orchards of North Central Washington. Am Med Assoc Arch Indust Hygiene 1954: 10: 522–529.

    CAS  Google Scholar 

  • Bernard C.E., Nuygen H., Truong D., and Krieger R.I. Environmental residues and biomonitoring estimates of human insecticide exposure from treated residential turf. Arch Environ Contam Toxicol 2001: 41: 237–240.

    Article  CAS  Google Scholar 

  • Carmichael N.G. Pesticide exposure: overview of the tiered approach. In: : Proceedings of the Workshop on Methods of Pesticide Exposure Assessment. October 5–8, 1993 Ottawa, Canada, 1995.

    Google Scholar 

  • Carmichael N.G., Nolan R.J., Perkins J.M., Davies R., and Warrington S.J. Oral and dermal pharmacokinetics of triclopyr in human volunteers. Hum Toxicol 1989: 8: 431–437.

    Article  CAS  Google Scholar 

  • Chester G. Revised guidance document for the conduct of field studies of exposure to pesticides in use. In: Curry P.B., Iyengar S., Maloney P.A., and Maroni M. (eds.). Methods of Pesticide Exposure Assessment. Plenum Press, New York, 1995.

    Google Scholar 

  • Chester G. Evaluation of agricultural worker exposure to, and absorption of, pesticides. Ann Occup Hyg 1993: 37: 509–523.

    CAS  PubMed  Google Scholar 

  • Chester G., and Hart T.B. Biological monitoring of a herbicide applied through backpack and vehicle sprayers. Toxicol Lett 1986: 33: 137–149.

    Article  CAS  Google Scholar 

  • Chester G., and Ward R.J. An accurate method for measuring potential dermal exposure to pesticides. (Abstract) Hum Toxicol 1983: 2 (3): 555–556.

    Google Scholar 

  • Chester G., Dick J.P., Earl M., Marsh J.R., and Woollen B.H. Tralkoxydim: exposure of and absorption by workers using “Achieve” DF, 1991. ICI Agrochemicals No TMF 3587.

  • Chester G., Dick J.P., Loftus N.J., and Woollen B.H. Fluazifop-P-butyl: dermal exposure of and absorption by workers using tractor sprayers in the Netherlands, 1989. ICI Agrochemicals Report No TMF 3487.

  • Chester G., Gurunathan G., Jones N., and Woollen B.H. Occupational exposure of Sri Lankan tea plantation workers to paraquat. Bull. World Health Organization 1993: 71: 625–632.

    CAS  Google Scholar 

  • Conover W.J. Practical Nonparametric Statistics. John Wiley & Sons, Inc., New York, USA, 1999.

    Google Scholar 

  • Cowell J.E., Danhaus R.G., Kunstman J.L., Hackett A.G., Oppenhuizen M.E., and Steinmetz J.R. Operator exposure from closed system loading and application of alachlor herbicide. Arch Environ Contam Toxicol 1987: 16: 327–332.

    Article  CAS  Google Scholar 

  • Cowell J.E., Lottman C.M., and Manning M.J. Assessment of lawn care worker exposure to DTP. Arch Environ Contam Toxicol 1991: 21: 195–201.

    Article  CAS  Google Scholar 

  • Driver J., Ross J., Mihlan G., Lunchick C., and Landenberger B. Derivation of single-layer clothing penetration factors from the pesticide handlers exposure database. Toxicol Pharmacol 2007: Accepted for publication in Reg.

  • Dubelman S., and Cowell J.E. Biological monitoring technology for measurement of applicator exposure. In: Wang R.G.M., Franklin C.A., Honeycutt R.C., Reinert J.C. (eds.). Biological monitoring technology for pesticide exposure. ACS Symposium Series No.382 1989, pp. 240–250.

  • Duggan A., Charnley G., Chen W., Chukwudebe A., Hawk R., Ross J., Krieger R.I., and Yarborough C. Di-alkyl phosphate biomonitoring data: Assessing cumulative exposure to organophosphate pesticides. Reg Pharmacol Toxicol 2003: 37: 382–395.

    Article  CAS  Google Scholar 

  • Durham W.F., and Wolfe H.T. Measurement of the exposure of workers to pesticides. Bull WHO 1962: 26: 75–91.

    CAS  PubMed  Google Scholar 

  • Feldmann R.J., and Maibach H.I. Percutaneous penetration of some pesticides and herbicides in man. Toxicol Appl Pharmacol 1974: 28: 126–132.

    Article  CAS  Google Scholar 

  • Fenske R.A. Correlation of fluorescent tracer measurements of dermal exposure and urinary metabolite excretion during occupational exposure to malathion. Am Ind Hyg Assoc J 1988: 49: 438–444.

    Article  CAS  Google Scholar 

  • Fenske R.A. Validation of environmental monitoring by biological monitoring, Fluroescent tracer technique and patch technique. In: Wang R.G.M., Franklin C.A., Honeycutt R.C., Reinert J.C. (eds.). Biological monitoring for pesticide exposure, Measurement, estimation and risk reduction 1989. ACS Symposium Series 382. pp. 70–84.

  • Fenske R.A. Nonuniform dermal deposition patterns during occupational exposure to pesticides. Arch Environ Contam Toxicol 1990: 19: 332–337.

    Article  CAS  Google Scholar 

  • Findlay M.L. Diquat: worker exposure during mixing, loading and application of Reglone® with knapsack sprayers, 1998. Zeneca Ag Products Report No. RR97-004B.

  • Findlay M.L., and Wiseman J.M. Lambda-cyhalothrin: worker exposure during mixing, loading and application of a 50 g/kg wettable granule formulation to orchards with tractor-mounted air-assisted sprayers, 2000. Zeneca Agrochemicals Report No. WER 005.

  • Forbess R.C., Morris J.R., Lavy T.L., Talbert R.E., and Flynn R.R. Exposure measurements of applicators who mix and spray paraquat in grape vineyards. HortScience 1982: 17 (6): 955–956.

    Google Scholar 

  • Grover R., Franklin C.A., Muir N.I., Cessna A.J., and Riedel D. Dermal exposure and urinary metabolite excretion in farmers repeatedly exposed to 2, 4-D amine. Toxicol Lett 1986: 33: 73–83.

    Article  CAS  Google Scholar 

  • Honeycutt R.C. Use of simultaneous biological monitoring and dermal dosimetry techniques to detemine the exposure of chlorpyrifos to applicators and reentry workers. In: Honeycutt R.C., Day E. (eds.). Worker Exposure to Agrochemicals-Methods for Monitoring and Assessment. Published by Lewis, 2000.

    Google Scholar 

  • Honeycutt R.C., and Day E.W. Worker reentry exposure to chlorpyrifos in citrus treated with “Lorsban formulation 4E” insecticide, 1993. DowElanco Study ID 91-102HE.

  • Honeycutt R.C., and Day E.W. Evaluation of the potential exposure of workers to chlorpyrifos during mixing and loading, spray application and clean-up procedures during the treatment of citrus groves with chlorpyrifos formulation 4E insecticide, 1994. DowElanco Study ID 91-101HE.

  • Knaak J.B., Al-Bayati M.A., Raabe O.G., Wiedmann J.L., Pensyl J.W., Ross J.H., Leber A.P., and Jones P. Mixer-Loader-Applicator exposures and percutaneous absorption studies involving eptc herbicide: safety related to exposure. In: Biological Monitoring for Pesticide Exposure. American Chemical Society Symposium Series 382, Washington, D.C., 1989.

    Google Scholar 

  • Knuteson J.A., Barnekow D.E., Cook W.L., and Meitl T.J. Evaluation of Potential Exposure To Workers Mixing and Loading Lorsban Formulation 4E Insecticide Products for Aerial Application. Dow AgroSciences, LLC, Indianapolis, IN, 1999. Study ID HEA97038.

    Google Scholar 

  • Krieger R.I., Dinoff T.M., and Peterson J. Human disodium octaborate tetrahydrate (dot) exposure following carpet flea treatment not associated with significant dermal absorption. J Expos Anal Environ Epidemiol 1996: 6: 279–288.

    CAS  Google Scholar 

  • Krieger R.I., and Dinoff T.M. Captan fungicide exposures of strawberry harvesters using THPI as a urinary biomarker. Arch Environ Contam Toxicol 2000: 38: 398–403.

    Article  CAS  Google Scholar 

  • Krieger R.I., Dinoff T.M., Fell L., Osimitz T.G., Ross J.H., and Thongsinthusak T. Biomonitoring and whole body cotton dosimetry to estimate the potential human dermal exposure to semivolatile chemicals used indoors. J Expos Anal Environ Epidemiol 2000: 10: 50–57.

    Article  CAS  Google Scholar 

  • Kromhout H., and Vermeulen R. Temporal, personal and spatial variability in dermal exposure. Ann Occup Hyg 2001: 45: 257–273.

    Article  CAS  Google Scholar 

  • Lavy T., Cowell J.E., Steinmetz J.R., and Massey J.H. Conifer seedling nursery worker exposure to Glyphosate. Arch Environ Contam Toxicol 1992: 22: 6–13.

    Article  CAS  Google Scholar 

  • Lavy T.L., Shepard J.S., and Mattice J.D. Exposure measurements of applicators spraying (2,4,5-trichlorophenoxy) acetic acid in the forest. J Agric Food Chem 1980: 28: 626–630.

    Article  CAS  Google Scholar 

  • Maddy K.T., Edmiston S., and Richmond D. Illness, injuries, and deaths from pesticide exposures in California 1949–1988. Rev Environ Contam Toxicol 1990: 114: 57–123.

    CAS  PubMed  Google Scholar 

  • Murphy P.G., Beard K.K., Marino T.A., Myers C.R., Ormand J.R., and Timchalk C. Evaluation of chlorpyrifos exposures to workers during loading and application of “Lorsban formulation 15G Granular Insecticide” during corn planting, 1998. Dow Chemical Company Report HEH 311.

  • NAS (National Research Council). Human Biomonitoring for Environmental Chemicals. Committee on Human Biomonitoring for Environmental Toxicants, Board on Environmental Studies and Toxicology, Division of Earth and Life Sciences, National Research Council. The National Academy Press, Washington, D.C., 2006.

  • National Research Council. National Academy of Sciences. Risk Assessment in the Federal Government: Managing the Process. National Academy Press. Washington, D.C., 1983, pp. 1–191.

  • Nolan R.J., Rick D.L., Freshour N.L., and Saunders J.H. Chlorpyrifos: pharmacokinetics in human volunteers following single oral and dermal doses. Toxicol Appl Pharmacol 1984: 73: 8–15.

    Article  CAS  Google Scholar 

  • Nomiyama K., and Nomiyama H. Respiratory retention, uptake, and excretion of organic solvents in man. Int Arch Arbeitsmed 1974: 32: 75–83.

    Article  CAS  Google Scholar 

  • OECD Guidance Document for the Conduct of Studies of Occupational Exposure to Pesticides During Agricultural Application. OECD Environmental Health and Safety Publications. Series on Testing and Assessment No. 9. OECD/GD(97)148, 1997.

  • Ramsey J.D., Woollen B.H., Auton T.R., Batten P.L., and Leeser J.E. Pharmacokinetics of fluazifop-butyl in human volunteers. II: dermal dosing. Hum Exp Toxicol 1992: 11: 247–254.

    Article  CAS  Google Scholar 

  • Rosenheck L.A. Evaluation of diazinon exposure monitoring data and risk assessment for homeowners mixing, loading and applying the liquid formulation of diazinon to residential outdoor sites, 2000. Novartis Study Number 1063–00.

  • Ross J.H., and Driver J.H. Evaluation of exposure values from PHED compared with those derived from biological monitoring, 2006. Draft Report.

  • Ross J.H., Driver J.H., Cochran R.C., Thongsinthusak T., and Krieger R.I. Could pesticide toxicology studies be more relevant to occupational risk assessment? Ann Occup Hygiene 2001: 45 (Suppl 1): 5–17.

    Article  Google Scholar 

  • Ross J.H., Driver J.H., Harris S.A., and Maibach H.I. Dermal absorption of 2, 4-D: a review of species differences. Reg Toxicol Pharmacol 2005: 41: 82–91.

    Article  CAS  Google Scholar 

  • Ross J.H., Fong H.R., Thongsinthusak T., Margetich S., and Krieger R.I. Measuring potential dermal transfer of surface pesticide residue generated from indoor fogger use: using the cdfa roller method, interim report II. Chemosphere 1991: 22: 975–984.

    Article  CAS  Google Scholar 

  • Ross J.H., Fong H.R., Thongsinthusak T., and Krieger R.I. Experimental method to estimate indoor pesticide exposure to children. In: Guzelian P.S., Henry C.J., and Olin S.S. (eds.). Symposium on Similarities and Differences of Adults and Children: Implications for Risk Assessment. ILSI Press, 1992, pp. 226–241.

    Google Scholar 

  • Ross J.H., Thongsinthusak T., Fong H.R., Margetich S., and Krieger R.I. Measuring potential dermal transfer of surface pesticide residue generated from indoor fogger use: an interim report. Chemosphere 1990: 20: 349–360.

    Article  CAS  Google Scholar 

  • Rotondaro A., and McKane E. Worker mixer, loader, applicator exposure to Ronilan® WP, 1992b. Pan-Ag Study Nos. EF-90-02 and AL-106.

  • Rotondaro A., and Schuster L. Worker mixer/loader, applicator exposure to Ronilan® DF, 1992a. Pan-Ag Study Number AE-91-504/BASF Study No 91164.

  • SAS. SAS/STAT® 91 User's Guide, Volume 2. SAS Institute, Inc. Cary, NC, USA, 2004.

  • Selim S., and Krieger R.I. Indoor human pyrethrins exposure: contact absorption, metabolism, and urine biomonitoring. In: Krieger R., Seiber J., Ragsdale N. (eds.). Assessing Exposures and Reducing Risks to People from the use of Pesticides. ACS Series Publication 951, Oxford University Press, 2006, pp. 125–140.

    Google Scholar 

  • Selman F. Evaluation of the potential exposure of workers to atrazine during commercial mixing, loading and spray application to corn, 1996. Ciba Geigy Corporation Report No ABR-95133.

  • Sexton K., Needham L.L., and Pirkle J.L. Human biomonitoring of environmental chemicals. Am Sci 2004: 92: 38–45.

    Article  Google Scholar 

  • Shurdut B.A., Murphy P.G., Nolan R.J., and McNett D.A. Lorsban formulation 4E and 50W insecticides: Assessment of the chlorpyrifos exposures to applicators, mixer/loaders, and reentry personnel during and following application to low crops, 1993. DowElanco DERBI No 6568.

  • Staiff D.C., Comer S.W., Armstrong J.F., and Wolfe H.R. Exposure to the herbicide, paraquat. Bull Environ Contam Toxicol 1975: 14: 334–340.

    Article  CAS  Google Scholar 

  • Thongsinthusak T., Ross J.H., and Meinders D. Guidance for the preparation of human pesticide exposure assessment documents (HS-1612). California Department of Pesticide Regulation, Sacramento, CA, USA, 1993.

    Google Scholar 

  • Thongsinthusak T., Ross J.H., Saiz S., and Krieger R. Estimation of dermal absorption using the exponential saturation model. Reg Toxicol Pharmacol 1999: 29: 37–43.

    Article  CAS  Google Scholar 

  • USEPA. Pesticide Assessment Guidelines, Subdivision U, Applicator Exposure Monitoring. US EPA, Washington, D.C., 1986.

  • USEPA. Series 875-Occupational and Residential Exposure Test Guidelines, Group B: Post Application Exposure Monitoring Test Guidelines. US Environmental Protection Agency, Office of Prevention, Pesticides, and Toxic Substances. Washington, DC, 1997.

  • USEPA. US Environmental Protection Agency, 1998. Health Effects Test Guidelines OPPTS 870.7485 Metabolism and Pharmacokinetics, Office of Prevention, Pesticides and Toxic Substances (7101), EPA 712–C–98–244.

  • Van der Jagt K., Tielemans E., Links I., Brouwer D., and van Hemmen J. Effectiveness of personal protective equipment: relevance of dermal and inhalation exposure to chlorpyrifos among pest control operators J. Occup Environ Hygiene 2004: 1: 355–362.

    Article  CAS  Google Scholar 

  • Van Wendel de Joode B.N., De Graaf I.A.M., Wesseling C., and Kromhout H. Paraquat exposure of knapsack spray operators on banana plantations in Costa Rica. Int J Occup Environ Health 1996: 2: 294–304.

    Article  Google Scholar 

  • West B.T., Welch K.B., and Galecki A.T. Linear Mixed Models. Chapman & Hall/CRC, Boca Raton, FL, USA, 2004.

    Google Scholar 

  • Wester R.C., and Maibach H.I. Animal models for percutaneous absorption. In: Wang R.G.M., Knaak J.B., Maibach H.I. (eds.). Health Risk Assessment: Dermal and Inhalation Exposure and Absorption of Toxicants. CRC Press, Boca Raton, FL, USA, 1993, pp. 89–103.

    Google Scholar 

  • Wester R.C., Maibach H.I., Bucks D.A.W., and Aufrere M.M. In vivo percutaneous absorption of paraquat from hand, leg and forearm of humans. J Toxicol Environ Health 1984: 14: 759–769.

    Article  CAS  Google Scholar 

  • Wester R.C., Sedik L., Melendres J., Logan F., Maibach H.I., and Russel I. Percutaneous absorption of diazinon in humans. Food Chem Toxicol 1993: 31: 569–572.

    Article  CAS  Google Scholar 

  • Williams R.L., Aston L.S., and Krieger R.I. Perspiration increased human pesticide absorption following surface contact during an indoor scripted activity program. J Expos Anal Environ Epidemiol 2004: 14: 129–136.

    Article  CAS  Google Scholar 

  • Williams R.L., Bernard C.E., and Krieger R.I. Human exposure to indoor residential cyfluthrin residues during a structured activity program. J Expos Anal Environ Epidemiol 2003: 13: 112–119.

    Article  CAS  Google Scholar 

  • Wojeck G.A., Nigg H.N., Stamper H.J., and Bradway D.E. Worker exposure to ethion in florida citrus. Arch Environ Contam Toxicol 1981: 10: 725–735.

    Article  CAS  Google Scholar 

  • Wojeck G.A., Price J.F., Nigg H.N., and Stamper J.H. Worker exposure to paraquat and diquat. Arch Environ Contam Toxicol 1983: 12: 65–70.

    Article  CAS  Google Scholar 

  • Wolfe H.R. Field exposure to airborne pesticides. In: Lee R.E. (ed.). Air Pollution from Pesticides and Agricultural Processes. CRC Press, Boca Raton, FL, 1976, pp. 137–161.

    Google Scholar 

  • Woollen B. Biological monitoring for pesticide absorption. Ann Occup Hyg 1993: 37: 525–540.

    CAS  PubMed  Google Scholar 

  • Woollen B., Marsh J., Laird W., and Leeser J. The metabolism of cypermethrin in man: differences in urinary metabolite profiles following oral and dermal administration. Xenobiotica 1992: 22: 983–991.

    Article  CAS  Google Scholar 

  • World Health Organization. Field surveys of exposure to pesticides. Standard Protocol 1982 VBC/82.1.

Download references

Acknowledgements

The authors acknowledge the financial support of the Agricultural Handlers Exposure Task Force with secondary support from the Antimicrobial Exposure Assessment Task Force II.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John Ross.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ross, J., Chester, G., Driver, J. et al. Comparative evaluation of absorbed dose estimates derived from passive dosimetry measurements to those derived from biological monitoring: Validation of exposure monitoring methodologies. J Expo Sci Environ Epidemiol 18, 211–230 (2008). https://doi.org/10.1038/sj.jes.7500591

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jes.7500591

Keywords

This article is cited by

Search

Quick links